South Asians have a much higher risk of diabetes compared to Europeans and investigators don't know why this is. Investigators think that South Asians' capacity to store fat safely under the skin is lower than Europeans, so they start to store fat around internal organs and in liver and muscle, and at lower body weights than Europeans. These increased levels of internal fat storage are thought to increase risk of diabetes.

The purpose of the study therefore is to investigate whether there are differences with weight gain and weight loss in fat storage, fat cell function and metabolic risk factors, in South Asians compared with Europeans. Investigators will compare South Asian and European men at the start of the study, after they have gained about 7% body weight, and again after they have lost 7-15% body weight (from peak weight) to see how gaining and losing weight affects fat storage within the body and the function of fat cells. Investigators will also assess the effect of weight gain and weight loss on metabolism, fitness and risk factors for diabetes and heart disease.

South Asians have about five times the risk of adult onset diabetes (high blood sugar) than Europeans and nearly one in five South Asian men in the United Kingdom have the disease. Diabetes is a serious disease that can lead to a number of adverse health consequences including heart disease, kidney disease and blindness and accounts for about 10% of all healthcare costs in the UK. Obesity is strongly linked to diabetes risk, but the adverse effect of getting fatter on diabetes risk is much higher in South Asians than Europeans. The purpose of this study is to understand why this is the case. When humans put on weight initially this fat is stored under the skin (subcutaneous fat). This is relatively safe. However, when the capacity of this under skin storage is exceeded, fat is stored internally within the tummy area (visceral fat) and in organs such as the liver and muscle, which is less safe and increases diabetes risk. Investigators think that South Asians' capacity to store fat safely under the skin is lower than Europeans, so fat is stored internally and in liver and muscle at lower body weights than Europeans. The purpose of this study is to investigate whether this occurs and why. To do this investigators will compare a group of South Asian and European men and see how gaining and losing weight affects fat storage within the body and the function of fat cells. Investigators will also assess the effect of weight gain and weight loss on metabolism, fitness and risk factors for diabetes and heart disease.

The study will include healthy men of normal weight aged between 18-45 year and of either white European or South Asian (both parent of Indian, Pakistani, Bangladesh or Sri Lankan origin) ethnic origin.

Body weight will be altered by initially gaining weight and then losing weight. To do this participants will initially have to eat more food for 4-6 weeks and then go on a diet combined with exercise for 12 weeks. Participation in the study will last around 5½ months in total.

During the study pictures of body fat stores will be taken using an MRI scanner, a biopsy/sample of tummy fat will be taken to look at the fat cells and physical fitness and body metabolism (the way the body deals with sugar, insulin and fat) will be measured. These measurements will be done at three different times: before gaining weight, once weight is gained, and after losing weight (and back to original weight). The measurements will give a detailed assessment of the changes in the body when gaining or losing weight.

The benefits of taking part in the study are receiving detailed feedback about fitness levels, body fat, dietary intake, blood pressure, cholesterol, blood sugar and level of "insulin resistance". Feedback about the overall study findings will also be provided.

In addition, the knowledge gained from participation may benefit people who are at risk of diabetes in the future by increasing our understanding of why South Asians are at increased risk of developing diabetes. It will also help guide future research investigating how to reduce this increased risk through lifestyle changes and may also help direct the development of medicines to prevent and treat diabetes groups at increased risk of the disease.

Possible disadvantages of the study are gaining 7% of body weight over 4-6 weeks. This is likely to temporarily induce negative metabolic changes. However, investigators are also supporting losing this weight (and hopefully more) in the weight loss phase of the study. There is no evidence that short-term weight gain of this nature causes any long-term adverse effects. Longer-term weight gain however is associated with an increased risk of diabetes, cardiovascular disease and high blood pressure. It is therefore important that investigators ensure participants return to original weight at the start of the study. Taking fat biopsies carries a small risk of minor bruising or an infection. Good sterile practice reduces this risk of infection and application of ice and pressure to the biopsy site reduces the risk of bruising. Blood sampling via the cannula may cause minor bruising or an inflammation of the vein. Some participants may feel faint when they give blood. One of the exercise tests will be at a maximal level and the possibility exists that, very occasionally, certain changes may occur during or shortly after the test. They include abnormal blood pressure, fainting or a change in the normal rhythm of the heartbeat. There is a small possibility that taking part in this study will reveal a health problem that patients already have such as high cholesterol or high blood pressure. If such a problem is revealed, investigators will ask permission to inform the participant's General Practitioner to receive clinically appropriate follow-up care.

This study is running for ~2.5 years from March 2015 and is based at the University of Glasgow. The study is being funded by the European Commission as part of the European Medical Information Framework (EMIF), called EMIF-Metabolic. This research will help investigators to better predict who is likely to be at risk of developing diseases such as diabetes and to develop new medicines to prevent and treat these diseases. More details about EMIF-Metabolic are available here: http://www.emif.eu/emif-meta/objectives.

Inclusion Criteria:

• Participants will be men of European (self-report of both parents of white European origin) or South Asian (self-report of both parents of Indian, Pakistani, Bangladeshi or Sri Lankan origin) with BMI <25 kg.m-2, who have been weight stable (± 2 kg) for >6 months.

Exclusion Criteria:

• Exclusion criteria will include diabetes (physician diagnosed or HbA1c ≥6.5% on screening), history of cardiovascular disease, regular participation in vigorous physical activity, current smoking, taking drugs or supplements thought to affect carbohydrate or lipid metabolism, or other significant illness that would prevent full participation in the study.